Background-Experimentally, isoflurane, a commonly used volatile anesthetic agent, mimics the cardioprotective effects of ischemic preconditioning via a mechanism that could involve the activation of protein kinase C. The present study was designed to assess the clinical relevance of this observation in patients undergoing elective CABG. Methods and Results-Twenty patients were included in the study. In 10 of them, preconditioning was elicited after the onset of cardiopulmonary bypass via a 5-minute exposure to isoflurane (2.5 minimum alveolar concentration), followed by a 10-minute washout before aortic cross-clamping and cardioplegic arrest. Ten case-matched control patients underwent an equivalent period (15 minutes) of prearrest isoflurane-free bypass. Outcome measurements included troponin I and creatine kinase-MB isoenzyme (until the third postoperative day) levels and the activity of ecto-5Ј-nucleotidase, which contributes to adenosine production and is considered to be a reporter of protein kinase C activation, as assessed in right atrial biopsy samples taken before bypass and at the end of the preconditioning protocol (or after 15 minutes of bypass in control patients Key Words: ischemia Ⅲ bypass Ⅲ anesthesia I schemic preconditioning is recognized as one of the most effective means of reducing cellular necrosis. As such, its implementation during cardiac surgery might be clinically relevant, particularly in high-risk patients in whom any additional myocardial ischemic injury induced with cardiopulmonary bypass and superimposed cardioplegic arrest can adversely affect postoperative outcome. Because in this setting it is particularly desirable to avoid an ischemic-type preconditioning stimulus, 1-3 extensive research is targeted toward identifying the pharmacological mediators of the preconditioning phenomenon in an attempt to exploit them therapeutically.There is compelling evidence that the preconditioning signal activates various membrane receptors, which triggers a signaling pathway leading to the activation of several kinases, 4 in particular, protein kinase C (PKC), 5 and the subsequent opening of ATP-dependent potassium channels, possibly at the mitochondrial level. 6,7 How opening of these channels elicits cardioprotection is not yet established but might involve the limitation of calcium influx, better control of cellular volume, or both. This scheme provides a framework for rationalizing interventions targeted at mimicking preconditioning and, in this perspective, makes logical the use, among other drugs, of potassium channel openers.Within this class of drugs, only nicorandil is currently available for human use. However, aside from the fact that nicorandil cannot be administered intravenously, this compound has marked nitrovasodilatory properties, which can be Circulation is available at http://www.circulationaha.org
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